Clinical features associated with correction of T-cell senescence: increased acute-phase response, amyloidosis and arthritis.
Two prominent features associated with immunosenescence are thymic involution and altered T-cell phenotype and responsiveness. We have shown previously that in CD2-fas transgenic mice, in which the Fas apoptosis molecule is constituatively expressed on T cells, T-cell senescence is greatly reduced. Using a different experimental approach, the relationship between T-cell senescence and apoptosis was analyzed on human PBMCs. The results indicate that there was increased apoptosis of CD45RO- (CD45RA+) T cells upon activation. We propose that this could account for the increase in CD45RO+ 'memory' T cells with aging in humans. Together these results are consistent with the notion that T-cell senescence is associated with altered apoptosis and decreased T-cell responsiveness. T-cell responsiveness remained high in CD2-fas transgenic aged mice, but there was no increase in overall life span of the mice. Increased T-cell responsiveness was associated with an increased acute-phase response and amyloid A deposition in the glomerulus of these mice. These data suggest that restoration of the T-cell immune function in aged individuals must be carried out in concert with correction of other immune factors that down modulate the acute-phase response to prevent undesirable side-effects.
Mountz
J D
JD
University of Alabama at Birmingham, Department of Medicine 35294-0007, USA. John.Mountz@ccc.uab.edu
Hsu
H C
HC
D000210:Acute-Phase Reaction / Q000276:immunology*; D000375:Aging / Q000276:immunology*; D000686:Amyloidosis / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D001168:Arthritis / Q000276:immunology*; D015551:Autoimmunity; D018801:CD2 Antigens / Q000235:genetics / Q000276:immunology; D016922:Cellular Senescence; D005544:Forecasting; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D009175:Mycoplasma Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology
D018801:CD2 Antigens; D019014:fas Receptor